tbuckley/cabot-search huggingface dataset:
FGFR2 Inhibition in Cholangiocarcinoma
Authors: Arndt Vogel, Oreste Segatto, Albrecht Stenzinger, Anna Saborowski
Journal: Annual Review of Medicine (2022)

Biliary tract cancer (BTC) is the second most common primary liver cancer after hepatocellular carcinoma and accounts for 2% of cancer-related deaths. BTCs are classified according to their anatomical origin into intrahepatic (iCCA), perihilar, or distal cholangiocarcinoma, as well as gall bladder carcinoma. While the mutational profiles in these anatomical BTC subtypes overlap to a large extent, iCCA is notable for the high frequency of IDH1/2 mutations (10–22%) and the nearly exclusive occurrence of FGFR2 fusions in 10–15% of patients. In recent years, FGFR2 fusions have become one of the most promising targets for precision oncology targeting BTC, with FGFR inhibitors already approved in Europe and the United States for patients with advanced, pretreated iCCA. While the therapeutic potential of nonfusion alterations is still under debate, it is expected that the field of FGFR2-directed therapies will be subject to rapid further evolution and optimization. The scope of this review is to provide an overview of oncogenic FGFR signaling in iCCA cells and highlight the pathophysiology, diagnostic testing strategies, and therapeutic promises and challenges associated with FGFR2-altered iCCA.
Personalized Therapeutics for K<sub>ATP</sub>-Dependent Pathologies
Authors: Colin G. Nichols
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Ubiquitously expressed throughout the body, ATP-sensitive potassium (K ATP ) channels couple cellular metabolism to electrical activity in multiple tissues; their unique assembly as four Kir6 pore-forming subunits and four sulfonylurea receptor (SUR) subunits has resulted in a large armory of selective channel opener and inhibitor drugs. The spectrum of monogenic pathologies that result from gain- or loss-of-function mutations in these channels, and the potential for therapeutic correction of these pathologies, is now clear. However, while available drugs can be effective treatments for specific pathologies, cross-reactivity with the other Kir6 or SUR subfamily members can result in drug-induced versions of each pathology and may limit therapeutic usefulness. This review discusses the background to K ATP channel physiology, pathology, and pharmacology and considers the potential for more specific or effective therapeutic agents.
Biased Agonism: Lessons from Studies of Opioid Receptor Agonists
Authors: Eamonn Kelly, Alexandra Conibear, Graeme Henderson
Journal: The Annual Review of Pharmacology and Toxicology (2022)

In ligand bias different agonist drugs are thought to produce distinct signaling outputs when activating the same receptor. If these signaling outputs mediate therapeutic versus adverse drug effects, then agonists that selectively activate the therapeutic signaling pathway would be extremely beneficial. It has long been thought that μ-opioid receptor agonists that selectively activate G protein– over β-arrestin-dependent signaling pathways would produce effective analgesia without the adverse effects such as respiratory depression. However, more recent data indicate that most of the therapeutic and adverse effects of agonist-induced activation of the μ-opioid receptor are actually mediated by the G protein–dependent signaling pathway, and that a number of drugs described as G protein biased in fact may not be biased, but instead may be low-intrinsic-efficacy agonists. In this review we discuss the current state of the field of bias at the μ-opioid receptor and other opioid receptor subtypes.
Sodium–Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study
Authors: Devin Abrahami, Helen Tesfaye, Hui Yin, Seanna Vine, Blánaid Hicks, Oriana H.Y. Yu, Lysanne Campeau, Robert W. Platt, Sebastian Schneeweiss, Elisabetta Patorno, Laurent Azoulay
Journal: Diabetes Care (2022)

OBJECTIVE To determine whether sodium–glucose cotransporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase 4 (DPP-4) inhibitors, are associated with an increased risk of early bladder cancer events. RESEARCH DESIGN AND METHODS We conducted a multisite, population-based, new-user, active comparator cohort study using the U.K. Clinical Practice Research Datalink, Medicare fee-for-service, Optum’s de-identifed Clinformatics Data Mart Database (CDM), and MarketScan Health databases from January 2013 through December 2020. We assembled two cohorts of adults with type 2 diabetes initiating 1) SGLT2 inhibitors or GLP-1RAs and 2) SGLT2 inhibitors or DPP-4 inhibitors. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% CIs of incident bladder cancer. The models were weighted using propensity score fine stratification. Site-specific HRs were pooled using random-effects models. RESULTS SGLT2 inhibitor (n = 453,560) and GLP-1RA (n = 375,997) users had a median follow-up ranging from 1.5 to 2.2 years. Overall, SGLT2 inhibitors were not associated with an increased risk of bladder cancer compared with GLP-1RAs (HR 0.90, 95% CI 0.81–1.00). Similarly, when compared with DPP-4 inhibitors (n = 853,186), SGLT2 inhibitors (n = 347,059) were not associated with an increased risk of bladder cancer (HR 0.99, 95% CI 0.91–1.09) over a median follow-up ranging from 1.6 to 2.6 years. Results were consistent across sensitivity analyses. CONCLUSIONS Contrary to previous randomized controlled trials, these findings indicate that the use of SGLT2 inhibitors is not associated with an increased risk of bladder cancer compared with GLP-1RAs or DPP-4 inhibitors. This should provide reassurance on the short-term effects of SGLT2 inhibitors on bladder cancer incidence.
Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes
Authors: Steven J Russell, Roy W Beck, Edward R Damiano, Firas H El-Khatib, Katrina J Ruedy, Courtney A Balliro, Zoey Li, Peter Calhoun, R Paul Wadwa, Bruce Buckingham, Keren Zhou, Mark Daniels, Philip Raskin, Perrin C White, Jane Lynch, Jeremy Pettus, Irl B Hirsch, Robin Goland, John B Buse, Davida Kruger, Nelly Mauras, Andrew Muir, Janet B McGill, Fran Cogen, Jill Weissberg-Benchell, Jordan S Sherwood, Luz E Castellanos, Mallory A Hillard, Marwa Tuffaha, Melissa S Putman, Mollie Y Sands, Gregory Forlenza, Robert Slover, Laurel H Messer, Erin Cobry, Viral N Shah, Sarit Polsky, Rayhan Lal, Laya Ekhlaspour, Michael S Hughes, Marina Basina, Betul Hatipoglu, Leann Olansky, Amrit Bhangoo, Nikta Forghani, Himala Kashmiri, Francoise Sutton, Abha Choudhary, Jimmy Penn, Rabab Jafri, Maria Rayas, Elia Escaname, Catherine Kerr, Ruby Favela-Prezas, Schafer Boeder, Subbulaxmi Trikudanathan, Kristen M Williams, Natasha Leibel, M Sue Kirkman, Kate Bergamo, Klara R Klein, Jean M Dostou, Sriram Machineni, Laura A Young, Jamie C Diner, Arti Bhan, J Kimberly Jones, Matthew Benson, Keisha Bird, Kimberly Englert, Joe Permuy, Kristina Cossen, Eric Felner, Maamoun Salam, Julie M Silverstein, Samantha Adamson, Andrea Cedeno, Seema Meighan, Andrew Dauber
Journal: New England Journal of Medicine (2022)

Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.
Treatment and Prevention of Heat-Related Illness
Authors: Cecilia Sorensen, Jeremy Hess
Journal: New England Journal of Medicine (2022)

A 71-year-old man with a history of coronary artery disease, congestive heart failure, and schizoaffective disorder presents to the emergency department with confusion.On the day of presentation, he was seen walking near his apartment complex in a busy urban area and was later found collapsed outside his building.The local heat index (accounting for temperature and relative humidity) is 105°F (40.6°C).On arrival in the emergency department, he is conscious but confused.His heart rate is 130 beats per minute, blood pressure 100/70 mm Hg, respiratory rate 28 breaths per minute, rectal temperature 40.5°C, and oxygen saturation 90% while he is receiving oxygen at a rate of 3 liters per minute through a nasal cannula.He opens his eyes to voice and can state his name.He is able to move his arms and legs and has no focal neurologic deficits.His skin is hot and dry to the touch.His medications include furosemide, risperidone, and carvedilol.The patient lives alone in a top-floor apartment without air conditioning.How should this heat-related illness be treated, and how could it have been prevented?The Clinic a l Problem C limate change is causing a global increase in average temperatures and increasing the frequency, duration, and intensity of extreme heat events, 1 resulting in unprecedented levels of heat exposure.The past 7 years have been the hottest on record, 1 and climate change either caused or dramatically worsened 2 recent extreme heat events in Europe (2022), 3 India (2022), 4 and the Pacific Northwest of the United States (2021). 5In the past 20 years, there has been a 54% increase in heat-related mortality among persons older than 65 years of age, 6 and more than one third of all global warm-season heat-related deaths are attributable to climate change. 7On our current global greenhouse gas emissions trajectory, with warming of 2°C over preindustrial temperatures expected by midcentury, most of the world is expected to encounter frequent extreme heat events in the coming decades 8 ; formerly once-in-10-years heat waves are projected to occur more than 5 times as frequently and once-in-50-years events almost 14 times as frequently. 2 Elevated global temperatures and heat waves are already increasing the global health burden and causing substantial economic loss. 1 Humans thermoregulate through behavioral and autonomic mechanisms (e.g., vasodilation and sweating) to maintain a core internal temperature of approximately 37°C.Metabolic activity generates an internal heat load, and exogenous heat from Fossil-Fuel Pollution and Climate Change
Seeking Simpler Solutions with Diabetes Technology
Authors: Jennifer Sherr
Journal: New England Journal of Medicine (2022)

In January 1922, the management of type 1 diabetes was forever altered when Leonard Thompson became the first person to receive an injection of insulin extract.1 Although treatment with insulin therapy has been possible for more than a century, providers and persons with type 1 diabetes are faced with the grim reality that the attainment of glycemic targets remains elusive for many, increasing the risk of microvascular and macrovascular complications.2 To aid with diabetes management, various technologies have been developed. Some are aimed at measuring glucose, with continuous glucose monitors that currently offer a plethora of data on which to . . .
Sickle Cell Disease and Gene Therapy — Patient and Physician Perspectives
Authors: Michael DeBaun, Matthew Heeney, Terry Jackson, Dan Longo, Melesa Love, Trinity Love, Phillip Okwo, Alexis Thompson, Cassandra Trimnell, Teonna Woolford
Journal: New England Journal of Medicine (2022)

In this short documentary video from the New England Journal of Medicine, patients and physicians partner both to highlight the experience of living with sickle cell disease and to discuss the pathophysiology of the disease and new treatment strategies, including gene therapy. Patients share their own stories of interactions with the health care system and explore the challenging topics of racial disparity and health equity. Physicians express a cautious optimism as they review the risks and benefits of gene therapy.
Case 30-2022: A Newborn Girl with Hypoglycemia
Authors: Sarbattama Sen, Sjirk J. Westra, Juan D. Matute, Jordan S. Sherwood, Frances A. High, Melanie C. Kwan
Journal: New England Journal of Medicine (2022)

A newborn girl was admitted to the neonatal ICU with prolonged hypoglycemia. At 34 weeks of gestation, an ultrasonographic survey of the fetal anatomy had revealed an intraabdominal cystic mass. A diagnostic test was performed.
BNT162b2 COVID-19 vaccination uptake, safety, effectiveness and waning in children and young people aged 12–17 years in Scotland
Authors: Igor Rudan, Tristan Millington, Karen Antal, Zoe Grange, Lynda Fenton, Christopher Sullivan, Audrey Buelo, Rachael Wood, Lana Woolford, Olivia V. Swann, Josephine L.K. Murray, Lucy A. Cullen, Emily Moore, Fasih Haider, Fatima Almaghrabi, Jim McMenamin, Utkarsh Agrawal, Syed Ahmar Shah, Steven Kerr, Colin R. Simpson, Srinivasa Vittal Katikireddi, Sir Lewis D. Ritchie, Chris Robertson, Sir Aziz Sheikh
Journal: The Lancet Regional Health - Europe (2022)
Sphingosine kinase 1 promotes growth of glioblastoma by increasing inflammation mediated by the NF-κB /IL-6/STAT3 and JNK/PTX3 pathways
Authors: Wan Li, Hongqing Cai, Liwen Ren, Yihui Yang, Hong Yang, Jinyi Liu, Sha Li, Yizhi Zhang, Xiangjin Zheng, Wei Tan, Guanhua Du, Jinhua Wang
Journal: Acta Pharmaceutica Sinica B (2022)
Placenta segmentation in ultrasound imaging: Addressing sources of uncertainty and limited field-of-view
Authors: Veronika A. Zimmer, Alberto Gomez, Emily Skelton, Robert Wright, Gavin Wheeler, Shujie Deng, Nooshin Ghavami, Karen Lloyd, Jacqueline Matthew, Bernhard Kainz, Daniel Rueckert, Joseph V. Hajnal, Julia A. Schnabel
Journal: Medical Image Analysis (2022)

Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US resulting in highly variable reference annotations, and (iii) the limited field-of-view of US prohibiting whole placenta assessment at late gestation. In this work, we address these three challenges with a multi-task learning approach that combines the classification of placental location (e.g., anterior, posterior) and semantic placenta segmentation in a single convolutional neural network. Through the classification task the model can learn from larger and more diverse datasets while improving the accuracy of the segmentation task in particular in limited training set conditions. With this approach we investigate the variability in annotations from multiple raters and show that our automatic segmentations (Dice of 0.86 for anterior and 0.83 for posterior placentas) achieve human-level performance as compared to intra- and inter-observer variability. Lastly, our approach can deliver whole placenta segmentation using a multi-view US acquisition pipeline consisting of three stages: multi-probe image acquisition, image fusion and image segmentation. This results in high quality segmentation of larger structures such as the placenta in US with reduced image artifacts which are beyond the field-of-view of single probes.
Modeling mucus physiology and pathophysiology in human organs-on-chips
Authors: Zohreh Izadifar, Alexandra Sontheimer-Phelps, Bob A. Lubamba, Haiqing Bai, Cicely Fadel, Anna Stejskalova, Alican Ozkan, Queeny Dasgupta, Amir Bein, Abidemi Junaid, Aakanksha Gulati, Gautam Mahajan, Seongmin Kim, Nina T. LoGrande, Arash Naziripour, Donald E. Ingber
Journal: Advanced Drug Delivery Reviews (2022)
Genome characterization of monkeypox cases detected in India: Identification of three sub clusters among A.2 lineage
Authors: Anita M. Shete, Pragya D. Yadav, Abhinendra Kumar, Savita Patil, Deepak Y. Patil, Yash Joshi, Triparna Majumdar, Vineet Relhan, Rima R. Sahay, Meenakshy Vasu, Pranita Gawande, Ajay Verma, Arbind Kumar, Shivram Dhakad, Anukumar Bala Krishnan, Shubin Chenayil, Suresh Kumar, Priya Abraham
Journal: Journal of Infection (2022)
Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment
Authors: Chansub Lee, Sungyoung Lee, Eunchae Park, Junshik Hong, Dong-Yeop Shin, Ja Min Byun, Hongseok Yun, Youngil Koh, Sung-Soo Yoon
Journal: Genome Medicine (2022)

Although anti-apoptotic proteins of the B-cell lymphoma-2 (BCL2) family have been utilized as therapeutic targets in acute myeloid leukaemia (AML), their complicated regulatory networks make individualized therapy difficult. This study aimed to discover the transcriptional signatures of BCL2 family genes that reflect regulatory dynamics, which can guide individualized therapeutic strategies.From three AML RNA-seq cohorts (BeatAML, LeuceGene, and TCGA; n = 451, 437, and 179, respectively), we constructed the BCL2 family signatures (BFSigs) by applying an innovative gene-set selection method reflecting biological knowledge followed by non-negative matrix factorization (NMF). To demonstrate the significance of the BFSigs, we conducted modelling to predict response to BCL2 family inhibitors, clustering, and functional enrichment analysis. Cross-platform validity of BFSigs was also confirmed using NanoString technology in a separate cohort of 47 patients.We established BFSigs labeled as the BCL2, MCL1/BCL2, and BFL1/MCL1 signatures that identify key anti-apoptotic proteins. Unsupervised clustering based on BFSig information consistently classified AML patients into three robust subtypes across different AML cohorts, implying the existence of biological entities revealed by the BFSig approach. Interestingly, each subtype has distinct enrichment patterns of major cancer pathways, including MAPK and mTORC1, which propose subtype-specific combination treatment with apoptosis modulating drugs. The BFSig-based classifier also predicted response to venetoclax with remarkable performance (area under the ROC curve, AUROC = 0.874), which was well-validated in an independent cohort (AUROC = 0.950). Lastly, we successfully confirmed the validity of BFSigs using NanoString technology.This study proposes BFSigs as a biomarker for the effective selection of apoptosis targeting treatments and cancer pathways to co-target in AML.
Current Medical Literature
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A 1969 Head Start Medical Program
Authors: Robert A. Hoekelman
Journal: JAMA (1972)

The health goals of Project Head Start were not accomplished in the Rochester, NY, 1969 Summer Head Start Medical Program. There are few available data to indicate whether these goals are being reached elsewhere. These failures and failures in reaching educational and social goals led to elimination of the Summer Head Start program in Rochester and to expansion of the year-round program. Health goals of Head Start programs and the methods of reaching them need alteration to increase prospects for success. The elimination of routine periodic physical examinations and the utilization of professional nurses as health care coordinators for children and their families is proposed as a means to conserve scarce medical manpower and to provide a mechanism for improved health care within Head Start programs and elsewhere.
The National Football Head and Neck Injury Registry
Authors: Joseph S. Torg
Journal: JAMA (1979)

The National Football Head and Neck Injury Registry has documented 1,129 injuries since 1971 that involved hospitalization for more than 72 hours, surgical intervention, fracture-dislocation, permanent paralysis, or death. Of this group of injuries, 550 were fracture-dislocations of the cervical spine, of which 176 were associated with permanent quadriplegia. It appears that during the last two decades, there has been a decrease in the incidence of direct fatalities, head injuries associated with intracranial hemorrhage, and injuries associated with death. Conversely, cervical spine injuries with fracture-dislocation and with permanent quadriplegia have increased. We believe that these observations are the result of the development of a protective helmet-face mask system that has effectively protected the head, and by so doing has allowed it to be used as a battering ram in tackling and blocking techniques, thus placing the cervical spine at risk of injury. (<i>JAMA</i>241:1477-1479, 1979)
Ocular Toxoplasmosis
Authors: Robert B. Nussenblatt
Journal: JAMA (1994)

<h3>SELECTED CASES</h3><h3>Case 1</h3> A 20-year-old man was seen in 1989 after 10 days of decreasing vision in the right eye. Four months previously, he had lost weight and had lymphadenopathy and fever, which lasted about 4 days. Ocular examination showed poor vision in the right eye (20/200), vitreal cells, and a focal necrotizing retinochoroiditis in the macula. His antitoxoplasmosis immunoglobulin M (IgM) and immunoglobulin G (IgG) titers were 1:256 and 1:32 000. He was treated with pyrimethamine, sulfadiazine, and prednisone, with a resolution of the lesion's activity. He was left with a scar in the macula, and his vision improved to 20/40. In 1991, he developed a small satellite lesion close to the original one and was retreated. His IgG titer was 1:512, and the IgM titer was negative. <h3>Case 2</h3> In 1978, a 2-year-old boy living in southern Brazil developed a fever that lasted for 3 weeks. Systemic
A Model of Its Kind
Authors: A. McGehee Harvey
Journal: JAMA (1989)

WITH this ringing invocation, John Shaw Billings ended his speech at the opening of The Johns Hopkins Hospital on May 7, 1889. As the individual most responsible for designing and planning the hospital, Billings was one of the key speakers. Yet his words were not mere congratulatory phrases, appropriate for an event that commemorated the end of his years of effort. In the century since the hospital's opening, Billings' hope was fulfilled, as Hopkins became a model for American medical practice, education, and research. This model was not a composite of entirely new concepts and methods, however, but a cohesive, effective union of ideas, several of which had already been tried elsewhere. In the stimulating environment created by the early leaders of Hopkins, these ideas were merged in a novel way. <h3>ANTECEDENTS OF THE HOPKINS MODEL</h3> William H. Welch credited the advances in medical education made by Hopkins' predecessors: The